Teb same



other does not represent Patented May 12, 1931 ERNST PBEISRVEEK, 033 BA.

L, SE1

tassel END, TD HGFFMAN-LA RQCHE INC OF NEVJ'ARK, NluVJ' JERSEY, ll. GOREOBATION NEW JERSEY COMPOUND 01? DIALKYL BARBE'EUBFC ACIDS AND PROCESSES FOR MAKING THE SAME No Drawing. Original application filed July 10, 1925, Serial No. 42,828, and in Switzerland July 23, 1924.

Divided and.

My invention relates to new compounds of certain dialkyl barbituric acids and 1-pl.enyl- 2.3 dimethyl -4 dithylamino 5 pyrazolone and processes for makingthe same.

These compounds hare the general for- R and B being the same or two diiierent allryl groups but in any compo nd in which either represents the iso propyl group the the allyl group. in my United States Letters Patent No. 1,494,127, I have described the process of melting together one molecule oi iso propyl allyl barbituric acid with 1 molecule of 1- phenyl-Q.3-dimethyl- 4 dimethylamino-o-pyrazolone and the new compound produced therebywhich contains these two constituents in molecular proportion.

I am aware of the fact that methods for producing compounds of certain 'dialkyl barbituric acids and 1-phenyl-2.3-dimethyl- 4-dimethylamino-5-pyrazolone have been dis closed, which compounds were made by causing a reaction between one molecule of the acid and two molecules of l-phen l-Qfiidimethyl-4-dimethylamino-5 pyrazolone. (See United States patents to Starlrenst-ein No. 1,459,347, Volwiler No. 1,478,463 and Thiele Nos. 1,530,021 and 1,588,554). These substances are therefor either true compounds containing one molecule of the acid and two molecules of 1-phenyl-2.3-dimethyl-4- dimethylamino-5-pyrazolone or are mixtures of 1-phenyl-2.8-dimethyl-4-dimethylamino-5- pyrazolone with a compound containing the two constituents in molecular proportion. In the former case they are not the cor-.- pounds of my present invention and in the latter they comprise a mixture of one of my compounds with l-phenyl-Q.3-dimethyl-4-dimethylamino-5-pyrazolone disclosed under such circumstances that it was not known that my compounds could be produced.

I may produce my compounds either by melting together the two ingredients in me this application filed December 1'2, 192?.

. and are of value as medicines.

Serial No. 240,939.

lecular proportion or by dissolving them in a common solvent in any proportions and permitting the resulting compound to separate by precipitation. By a common solvent I mean a liquid medium in which both constituents will dissolve and which will permit precipitation of the specified compound. When 1 cause the ingredients to react in a common solvent the excess of either ingredient will remain in solution when the pure compound is precipitated. The new compounds when obtained by crystallization form clearly defined crystals. They are easily soluble in most of the organic solvents Example 1 .231 parts of 1-phenyl-2.8-dimethyl-4- dimethylamino-5-pyrazolone are mixed with 212 parts of dipropyl barituric acid and heated to about 110 C. in a para'liin bath. is soon as the melt is clear, it is poured into a cup and stirred until it solidifies to yellow crystal cake. Jitter complete cooling this calre is broken up and ground. A bright yellow powder is obtained, which has a neutral reaction and melts at 9192 C.

Example 2 208 parts of diallyl barbituric acid and 231 parts of l-pnenyl-Q.3-dimethyl-4-dimethylamino5-pyrazolone are heated in an oil bath of -30140 0., until a clear melt is obtained. The homogeneous melt is cooled to about {1, it necessary seeded and stirred. It solidifies to a firm yellow cake. hen cold this calre isbrol-ten up and ground.

it will be noted that in the examples, in which the ingredients are melted together, they are present in molecular proportion.

in this application 1 do not claim the specific process of causing isopropyl allyl barbituric acid to react with l-phenyl-Qfi-dimethyl 4 dimethylamino 5 pyrazolone nor the product of such specific process. My

United States Letters Patent No. 1,494,127,

of making my new compounds in isolate condition, and specifically the process of making my new compounds by melting them toge in molecular proportions hut do no specifically the reaction in so larly as this method is cover broadly in my cope No. 412,826, filed Ju \Vhile so all dialled burl l-phcnyl -23 c pyrazolone to r n l y desire it to he unders'too' more of such acids u are not to be regu doe. as ll claims. hen in my claims I c specified subgroup of dial; I intend to refer to all any which may he plained and excepting turie acid.

Broadly speaking my view it is based uron dialkyl harhituric acirs only isopropyl allyl he pahle of forming com I new 2.3-dimctl yl-l-dimet 'ZOl ,7 in which these CO1. c pre...e-

in molecular proportions. g was not ob vious from the dis T "l States Letters Patent llo. alkyl harbituric acids oth allyl harhituric a .'d would 1 pounds is clea ly shown hy r patents to others here aahove 1 either do not d'. close such coropou' they do disclose then'u do not reco existence and do not making them in a pure s mixture with an OXC dimcthylA-dimethylaiurn05-1 j l gredient.

My discovery valuable not merely he cause by means of it I may produce 1 numher oi therapeutically useful compounds of dialkyl harhituric acid and 1phenyl-2.3-dimethyl 4 dimethylam'no-5-pyrazolone but also because the im "cdicnts are recognized as he ins: present in molecular proportions. The acid ingredient makes the compoun d valuable as a hypnotic while the 1-phenyl-2.8-dimethyl-e-dimethylamino-S-pyrazolone ingredient makes it valuable as an analgesic and the compounds therefore possess the valuable property of being both a? algesic and hypnotic. Any compound which may contain the con stituents in the proportion of 1 molecular part of the acid (hypnotic) to two molecular parts of l-phenyl-2.3-dimethyll-dimethylamino-o pyrazolonc (analgesic) would exert a much greater analgesic etliect in proportion to the hypnotic effect than would my com pounds. If a physician should desire to pr0- dues in any one patient a higher proportion of analgesic effect to hypnotic effectthan is disclo e possible for such patient with any one of my compounds, he may produce this by adding thereto a suitable amount of l-phenyl-2.3-dimethyl-4:-dimethylamino 5 pyrazolone and this amount he may vary within any desired ll d more particularly without adding ooune an amount of 1-phenyl-2.3- "'hyl 4; din'iethylamino 5 pyrazolone equal to or greater than the amount of said ingredient already embodied in such compound. Chviously with a compound which 'eady contains two molecular parts of l-phcnyl 2.3 dimethyl-d-dimethylamino-iipyrazolone to one molecular part of the acid he mie'ht. in many, if not in most cases. be compelled to use more than the desired additio? el amount of analgesic. The same would he u no if the processes for which it is claimed that they produce such a compound, in fact ce only a mixture of a compound con- -i 5; the constituents in molecular proportion and an excess of one molecular part of l-phenylQB-dimethyl t dimethylamino-5- p n zolone, if such fact were recognized.

i do not claim the specific process of causin iethyl barbituric acid to react with 1 'l 2.3-dimethyl-4%-dimethylamino-5-pyrazolonc, or the product of such specific process, because I have been shown, in an interference proceeding; in which this application has been involved, an application by another inventor which in accordance with the relevant statute is entitled to priority with respect to this specific process and product.

mnle :2 shows that I use the word dialkyl covering both the saturated and the unsaturated radical; in other words, that I cover broa dly by this term the monovalent aliphatic hydrocarbon radicals.

I claim:

1. As new products, the isolated compounds of the general formula the followin formula myoo o0 l HNCO R and B being the same or two different alkyl groups but in any compound in which either represents the isopropyl group the other does not represent the allyl group and in any compound in which either represents the ethyl group the other does not represent the ethyl with no more than one molecule of group,

- dimethylamino-5- l-phenyl-2.3-dimethyl 4 pyrazolone.

3. As a new composition of matter a l'IllX- ture of compounds such as specified in claim ERNST PREISWERK. 

